Our research has confirmed that groups of patients with juvenile onset diabetes can be differentiated from each other and from normal children by the interactive patterns of their major carbohydrate and lipid regulatory hormones and biochemical data analyzed by clustering techniques based on principal components and regression coefficients. We propose to define the progression of the metabolic abnormalities in newly diagnosed diabetics from the time of diagnosis, through the remission period and during the relapse phase. Timed serial measurements of glucagon, insulin, cortisol, growth hormone and plasma and urine catecholamines and key biochemical data will be obtained during 26 hours of study of each patient in these 3 periods. The relationship between insulin reserves (C-peptide), islet cell antibodies, regulatory hormones and glucose homeostasis including assessment of Hb A1C will be analyzed statistically. The effect of catecholamine excess and alpha adrenergic blockade on beta cell function will be studied. The ability of beta adrenergic blockade to reduce the effects of catecholamine excess on lipolysis and ketogenesis will be investigated in patients with recurrent stress-induced ketoacidosis. The effect of the regulatory hormones on the metabolic state versus the effect of the metabolic state on the hormone patterns will be clarified in groups of previously diagnosed diabetics. The influence of the regulatory homones on the concentration of circulating metabolic intermediaries and on glucose and lipid homeostasis will be defined in the various study groups. All the variables obtained from the proposed studies will be entered into a data bank and their significance evaluated using clustering techniques based on principal component analysis of the regression coefficients or means. Efforts will be made to establish a statistical method, based on multivariable analysis, to quantitate the differences in severity of each patient's hormonal and biochemical abnormalities expressed as a distance measure between the patient and the normal. This will permit us to define in physiologic terms whether a patient is approaching or being driven further away from the normal state by a given mode of therapy.